The purpose of this R21 application is to explore a new hypothesis about the transmission of mother-child antisocial behavior disorders (ABDs). Women with ABDs are 4-8 times more likely than other mothers to have boys and girls who develop ABDs. This study is significant in that it will advance knowledge about mechanisms of mother-child transmission of ABDs, an understudied, important gap in research about a pernicious group of disorders that have major negative effects on society. These preliminary data will, through the next, larger longitudinal study, open up a new avenue of ABDs prevention research. Our Core Hypothesis is based on the Predictive Adaptation Response Hypothesis. We postulate that women with ABDs have stress response system (SRS) hypoactivity during pregnancy and that this programs SRS hypoactivity in the offspring, preparing the offspring for a postnatal environment that is stable, predictable, and rich in resources. In contrast, many mothers with ABDs are only able to provide a postnatal environment that is chaotic at best and overtly destructive to the offspring at worst. This mismatch promotes persistence of an immature, hypoactive SRS, which is characteristic of males and females with ABDs. Animal studies indicate that early postnatal brain development in an environment of endogenous SRS hypoactivity impedes the development of inhibition, can facilitate retention of primitive aggression, and result in learning difficulties, all characteristics of early onset ABDs. The impact of our study is that prevention work with this group of mothers would be substantially changed. For example, prevention work could begin during pregnancy in mothers identified as having ABDs; current parenting programs that start when children are in school may be too late. Specific Aims are to: 1) characterize SRS (hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS)) function in pregnant women with ABDs, compared to pregnant women without any psychiatric disorder (ND); 2) characterize SRS function of offspring in the first 4 months of life; 3) test a meditational hypothesis of maternal SRS function as the mechanism for the relationship between ABDs in mothers and infant SRS hypoactivity. To accomplish these aims, we will conduct a longitudinal study of 64 pregnant women (50% with ABDs), ages 16-30 years, and their infants until they are 4 months old, collecting data about mother and then infant SRS function at multiple points in time. This study is innovative in applying the Predictive Adaptation Response Hypothesis to the clinical problem of mother-child ABDs transmission and in its approach of measuring both components of the SRS. PUBLIC HEALTH RELEVANCE: This R21 application explores a new hypothesis about the mother-child transmission of antisocial behavior disorders. We hypothesize that mothers with antisocial behavior disorders have hypoactive stress response systems when they are pregnant and that this programs stress response system hypoactivity in the offspring. This hypoactivity in the infants could then facilitate the development of later antisocial behavior disorders.